Abstract
Mucosal melanoma is a rare and aggressive subtype of melanoma. Unlike its cutaneous counterpart, mucosal melanoma has only gained limited benefit from novel treatment approaches due to the lack of actionable driver mutations and poor response to immunotherapy. Over the last years, whole-genome and exome sequencing techniques have led to increased knowledge on the molecular landscape of mucosal melanoma. Molecular studies have underlined noteworthy findings with potential therapeutic implications, including the presence of KIT mutations, which are potential targets of tyrosine kinase inhibitors currently in use in the clinic (imatinib), but also SF3B1 mutation, CDK4 amplifications, and CDKN2A gene deletions, which are presently under investigation in clinical trials. Recent results from a pooled analysis of patients with mucosal melanoma treated with immunotherapy have suggested that the combination of immune checkpoint inhibitors might improve survival outcomes in this subset of patients, as compared with single-agent immunotherapy. However, these results are not confirmed across different studies, and combo-immunotherapy correlates with a higher rate of adverse events. In this review, we describe the clinical, biological, and genetic features of mucosal melanoma. We also provide an update on the results of approved systemic treatment in this setting and overview the therapeutic strategies currently under investigation in clinical trials.
Highlights
Publisher’s Note: MDPI stays neutralMucosal melanoma is a rare disease that is epidemiologically, biologically, and molecularly distinct from cutaneous melanoma [1]
Recurrent loss of sprout-related EVH1 domain containing protein 1 (SPRED1), a negative regulator of the mitogen-associated protein kinase (MAPK) pathway which acts by recruiting neurofibromin 1 (NF1) to the plasmatic membrane, has been found in 37% of 47 patients with mucosal melanomas, mostly of anorectal and vulvovaginal origin: this molecular alteration was mutually exclusive with NF1 mutations, which were found in 12% of patients [17]
The 5-year follow-up of 79 patients with mucosal melanoma from the CheckMate-067 trial showed that the combination of ipilimumab and nivolumab resulted in considerable higher objective response rate (ORR) compared with ipilimumab alone (43% vs. 7%), and in higher complete response rate (14% vs. 0%), and overall survival (OS) rate
Summary
Mucosal melanoma is a rare disease that is epidemiologically, biologically, and molecularly distinct from cutaneous melanoma [1]. We evidence suggests that the on prognosis of patients with mucosal melanoma has notin this setting and provide an update the results of approved systemic treatment improved as much as for cutaneous melanoma [8]. We provide an update on the results of approved systemic Methods treatment in this and overview the therapeutic strategies currently under investigation in clinical trials. We overview ongoing research and data of combination to identify ongoing clinical trialswhich enrolling patients with mucosal melanoma, both in the therapies currently under investigation, will impact future therapeutic strategies. The response lasted 3 years, the patient progressed and died These images come from the radiology archive of a patient with mucosal melanomas, as indicated in the “Materials and methods” section
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
